Parents' assessment of risk in sickle cell disease treatment with hydroxyurea

Hydroxyurea is the only medication shown to reduce the severity of sickle cell disease (SCD), but its long-term risks are unknown. Families of 58 children with SCD were interviewed on their perception of the potential risks of hydroxyurea treatment, and whether disease severity was a major factor in their treatment decision. Parents rated the severity of their child's SCD (86% as severe, 26% moderate, and 47% mild) and then the highest levels of risk that they would tolerate for both potential cancer (range 1/1,000 to 1/2) and potential birth defects (range 1/1,000 to 1/3) to benefit their child with hypothetical hydroxyurea treatment. Parents of 29 of the 58 children were unwilling to take any cancer risk whatsoever as a potential side effect of treatment, and 29 of 58 (not all the same parents) were unwilling to take any risk for birth defects, including half the children with severe SCD. For those families who did accept some risk, higher acceptable risk correlated with higher disease severity in the child (P = 0.04). The study's mixed findings highlight the complexities of risk perception and suggest that future studies of risks and benefits from the parental viewpoint are needed as candidate therapies are developed for SCD.     

Carbon dioxide clearance in rabbits during expiratory phase intratracheal pulmonary ventilation

The purpose of this study was to compare the efficacy of CO2 removal during conventional mechanical ventilation (CMV) with and without expiratory phase intratracheal pulmonary ventilation (expiratory ITPV or Exp-ITPV); and to compare CO2 clearance during Exp-ITPV, in pressure-controlled ventilation (PCV) and in volume-controlled ventilation (VCV) modes. Seven anesthetized rabbits were tracheotomized and intubated using a 4 mm endotracheal tube. Venous and arterial lines were established. The rabbits were paralyzed, mechanically ventilated, and ventilation parameters were adjusted to achieve baseline arterial hypercapnia. Animals were then ventilated during 30-minute trials of CMV and Exp-ITPV, in both PCV and VCV modes. A custom-built, microprocessor-controlled solenoid valve was used to limit ITPV gas flow to the expiratory phase. Proximal and carinal airway pressures and hemodynamic variables were continuously recorded, and arterial blood gases were analyzed at the end of each trial. Exp-ITPV, as compared with CMV, reduced arterial PCO2 by 12% and 21% in PCV and VCV modes, respectively (p < 0.02 and p < 0.001; one-sided paired t test), without significant changes in other cardiorespiratory variables. In conclusion, Exp-ITPV is more effective than CMV in clearing CO2 through a small endotracheal tube. Exp-ITPV is also more effective in VCV mode than PCV mode.